Project Summary/ Abstract: Cancer therapies are increasingly focusing on precision medicine and individualized therapies. In-vitro cell culture and in-vivo animal models are a critical resource for this research. However, most established cancer models lack comprehensive clinico-pathologic and molecular annotation and adequate representation of diverse patient populations and racial or ethnic minorities. Our proposal seeks to fill this gap by contributing gynecologic and breast cancer samples from African American women, a) leveraging the existing infrastructure of our gynecologic and breast cancer biorepositories, and b) capitalizing on the unique patient demographics of our Cancer Center?s catchment area within Northeast Ohio, comprising a significantly higher proportion of African American patients compared to the national average. The Case Comprehensive Cancer Center (Case CCC) is a consortium based at Case Western Reserve University (CWRU) linking all cancer-related research efforts at 3 independent institutions ? CWRU, University Hospitals and Cleveland Clinic. The catchment area of the Case CCC in Northeast Ohio includes approximately 23,000 new cancer cases per yearage-adjusted rate in the catchment area of 483 per 100,000 is higher than those for Ohio (455) and the US (448 per 100,000). Several women?s cancers, including endometrial, ovarian, and breast cancer demonstrate some of the greatest racial disparities in survival of all cancers. At present, biological mechanisms underlying this disparity are not well understood. While endometrial, ovarian and breast cancer-associated mortality is highest among African American women out of all racial groups, most genetic, genomic and epigenomic studies have focused on Caucasian/ European descendant populations, and any insight gained from these studies may only be applicable and benefit Caucasian women. The generation of novel in-vitro cancer models that adequately represent endometrial, ovarian and breast cancers from African American women are critically needed. The Gynecologic Biorepository and Breast Biorepository are integral components of the Women?s Cancer Initiative at Case CCC. This initiative has led to a racially diverse collection of >200 cryopreserved endometrial and ovarian cancer tumor tissue specimens since 2014, including samples from >70 African American women. Although more recent, the breast biorepository has had similar success and has already collected blood and tissue on >60 African American women in the last year. For this proposal, we will contribute a total of 35 biospecimens, comprising 12-14 endometrial, 10-12 ovarian, and 10-12 breast cancers from African American women. Less common subtypes (e.g. cervical, vulvar, or vaginal carcinomas, endometrial sarcomas, ovarian sex-cord-stromal tumors, primary breast angiosarcomas) will be included if available. This will result in improved racial diversity of next-generation cancer models as well as adequate representation across histologic and molecular subtypes.